Left ventricular assist devices for end-stage heart failure

The clinical and costeffectiveness of left ventricular

assist devices for end-stage heart
failure: a systematic review and
economic evaluation
AJ Clegg,1* DA Scott,2 E Loveman,1 J Colquitt,1
J Hutchinson,2 P Royle3 and J Bryant1
1

Southampton Health Technology Assessments Centre, Wessex Institute for

Health Research and Development, University of Southampton, UK
2
Fourth Hurdle Consulting Ltd, London, UK
3
University of Aberdeen, UK
* Corresponding author

Executive summary
Health Technology Assessment 2005; Vol. 9: No. 45

Health Technology Assessment

NHS R&D HTA Programme

HTA

Executive summary: Left ventricular assist devices for end-stage heart failure

Executive summary
Background
Heart failure is an increasing health problem in
England and Wales. Its incidence and prevalence
are increasing, leading to frequent admissions to
hospital and long-term drug costs. Concerns about
the effects on the duration and quality of life of
people and costs upon the NHS have resulted in
several government policy initiatives. End-stage
heart failure (ESHF) is associated with major
disability and a poor prognosis. Heart
transplantation has become the accepted form of
treatment for people with ESHF, improving
survival and patient quality of life. With continued
decreases in organ donation in England and
Wales, it is an option available to few. Mechanical
circulatory support through left ventricular assist
devices (LVADs) has attracted increased interest as
an option for patients with ESHF whether as a
bridge to heart transplantation (BTT), as a bridge
to myocardial recovery (BTR) or as a long-term
chronic support (LTCS). Continued developments
of LVADs, declining costs and improvements in
associated care have made their wider use a reality.

Objectives
The objectives of this study were to carry out a
systematic review and an economic evaluation to
examine the clinical and cost-effectiveness of
LVADS as a BTT, BTR and LTCS for people with
ESHF. The study focused on the effect of LVADs
on the duration and quality of life of people with
ESHF, the groups who may benefit from their use
and assesses the implications for developing such
a service within the NHS in England and Wales.

identify additional published and unpublished

references.

Study selection
Studies were included if they fulfilled the following
criteria:

Interventions: studies that evaluated currently

available LVADs used as a BTT, BTR and LTCS
for people with ESHF were considered for
inclusion.
Participants: people aged 16 years or older
with ESHF and considered suitable for receipt
of an LVAD as BTT, BTR or LTCS.
Outcomes: survival, functional capacity [e.g. New
York Heart Association (NYHA) functional
classification, activities of daily living] and quality
of life were the primary outcome measures
considered within the systematic review.
Design: systematic reviews, randomised
controlled trials (RCTs), controlled clinical trials,
cohort studies, case series, case studies, economic
evaluations and cost studies were included.

Studies identified were assessed for inclusion

through two stages with titles and abstracts and
full papers of retrieved studies assessed by two
reviewers, with differences in decisions resolved
through discussion or through recourse to a third,
independent reviewer.

Data extraction and quality assessment

A systematic review of the evidence and an

economic evaluation were undertaken using a
priori methods.

Data were extracted by two reviewers using data

extraction forms developed a priori, with any
disagreements resolved through discussion or
through recourse to independent assessment by a
third reviewer. The methodological quality of the
studies included in the systematic review of clinical
and cost-effectiveness were assessed using
recognised quality assessment tools using individual
components of methodological quality rather than
relying upon summary scores. The quality criteria
used were applied by two reviewers, with any
disagreements resolved through discussion or
through recourse to a third, independent reviewer.

Data sources

Data synthesis

Eighteen electronic databases were searched from

inception to October 2003. Bibliographies of
related papers were assessed for relevant studies
and experts and manufacturers were contacted to

Studies were synthesised using a narrative

approach through subgroup analysis based on
the indication for treatment, type of LVAD
and quality of studies.

Methods

Health Technology Assessment 2005; Vol. 9: No. 45 (Executive summary)

Economic evaluation
The economic evaluation developed two models to
evaluate the use of LVADs, first as a BTT and
second as LTCS for patients suffering from ESHF.
Insufficient data prevented the assessment of the
use of LVADS as a BTR. The outcomes in the
evaluation were assessed in terms of the benefits to
patients (survival and quality of life) and costs
incurred, with results presented in terms of a
costutility analysis. Although medical therapy was
the comparator treatment in the two models, the
patients differed. Patients in the BTT model were
those on the heart transplantation waiting list,
whereas those in the LTCS model were excluded
from the heart transplant waiting list owing to the
severity of their condition. The models focused on
those LVADs that were found in the systematic
review to be clinically effective for the different
indications and relevant to the UK setting.

Results
Clinical effectiveness of LVADs as
a BTT for people with ESHF
Sixteen studies (one controlled clinical trial, five
cohort studies with comparators, five cohort
studies with no comparator, three case series and
two case reports) assessed the clinical effectiveness
of LVADs as a BTT, 11 studies of first-generation
devices and five of second-generation devices. The
methodological quality of the studies was generally
weak, reflecting the quasi-experimental and
observational study designs used and poor
reporting of study characteristics. Despite the poor
quality evidence, LVADs compared with other
treatment options appeared to be beneficial for
patients with ESHF when assessed using patient
survival, functional status and quality of life. When
compared with inotropic agents, LVADs appeared
to provide a benefit in patient survival that
increased with the length of support (difference in
actuarial survival: 1 month 3%; 3 months 17%)
and extended beyond heart transplantation
(difference in actuarial survival: 1 year 24%;
4 years 30%). Comparisons of the use of LVADs
with usual care were less certain, with outcomes
varying from no difference in survival to, or after,
heart transplantation, to improved survival for
LVADs patients to heart transplantation (survival
difference: range 1459%) and post-transplantation
(difference in actuarial survival: 1 and 2 years
100%). Studies of LVADs which did not include a
comparator were often the only evidence available,
particularly for the new devices. In these studies,
implantation of an LVAD provided support for up
to 390 days, with as many as 70% of patients

surviving to transplantation. Comparisons of

different LVADs were limited. Only the HeartMate
and Novacor LVADs were compared, with little
difference in survival to transplantation. There was
limited evidence assessing the effects of LVADs on
the functional status and quality of life of patients
with ESHF BTT. Patients supported by an LVAD
appeared to have an improved functional status
compared with those on usual care. Also, patients
with an LVAD experienced an improvement in
their quality of life from before implantation of
the device to the period during support. The use
of LVADs is associated with risks of adverse events,
with patients suffering mechanical device failures,
bleeding, thromboembolic events, infections,
reoperations and psychiatric conditions. Adverse
events rates varied between different LVADs and
studies and some caution should be exercised in
interpreting these results. With a scarcity of
evidence directly comparing the different LVADs it
is difficult, and perhaps inappropriate, to identify
specific devices as the most clinically effective.
However, the HeartMate LVAD is the only device
that has evidence comparing it with several
different alternatives, appearing to be more
clinically effective than inotropic agents and usual
care and as clinically effective as the Novacor
device. Of the second-generation devices, the
evidence suggests limited difference in the clinical
effectiveness of the Jarvik 2000 and the MicroMed
DeBakey LVADs. Although early in their
development, these second-generation devices
appear to show lower rates of adverse events, such
as infection, bleeding and thromboembolism,
which have affected the development and use of
the first-generation devices. However, longer term
outcomes are needed to ensure that these
apparent benefits are maintained in practice and
that the consequences associated with the nonpulsatile nature of the devices do not result in
additional adverse events.

Clinical effectiveness of LVADs as a BTR

for people with ESHF
Evidence of the clinical effectiveness of LVADs as a
BTR for people with ESHF was limited to seven
non-comparative observational studies (two case
series and five case reports) of first-generation
devices, which were judged to be of poor
methodological quality. The seven identified
studies appeared to show that the LVADs provided
benefit in providing support for the patients until
myocardial recovery. As there were no direct
comparisons of different interventions, it is not
possible to assess whether the LVADs are more
effective than other alternatives or specific
devices. No evidence was found to judge the


Executive summary: Left ventricular assist devices for end-stage heart failure

effects of the devices on the quality of life or

functional status of patients. Limited information
on adverse events was reported, although
infections and bleeding were the main
concerns.

Clinical effectiveness of LVADs as

an LTCS for people with ESHF
Six studies (one RCT, one case series and four case
reports) assessed the clinical effectiveness of
LVADs as an LTCS for people with ESHF.
Although the nature and methodological quality
of the evidence varied between the different
devices, it was evident that LVADs provided
benefits for patients in terms of improved survival,
functional status and quality of life. The
REMATCH trial provided good-quality evidence
that the HeartMate LVAD provided a statistically
significant 48% reduction in the risk of death from
any cause when compared with optimal medical
management. Actuarial survival was significantly
higher for patients with the HeartMate LVAD
compared with optimal medical management at
1 year (52% versus 25%) and 2 years (23% versus
8%) follow-up. Importantly, improvements in
1-year survival were evident for patients aged
under 60 years and those aged 6069 years. Less
rigorous evidence for the Novacor, Toyobo and
Jarvik 2000 devices showed relatively high survival
(90%), with patients supported for up to 4 years.
Limited information on changes in patients
quality of life and functional status suggested that
patients experienced improvements on specific
scales following implantation of the HeartMate
and Jarvik LVADs. Inevitably there are adverse
events associated with the use of LVADs, with
device malfunctions, infection and bleeding
associated with their use. The HeartMate LVAD
was associated with twice as many serious adverse
events than optimal medical management, with
significantly higher rates of non-neurological
bleeding and neurological dysfunction. Other
adverse events affected the different treatment
options, whether devices or drug treatment.
Despite these adverse events, the benefits of these
LVADs appear to outweigh limitations. Evidence of
the clinical effectiveness of the different devices
indicates that the HeartMate LVAD appears to be
effective when compared with optimal medical
management. For the second-generation devices,
the early evidence suggests that the Jarvik 2000
shows promise; however, further research is
needed to assess whether these benefits are
replicated in the longer term and whether there
will be any long-term consequences associated with
the change in the nature of the circulatory
support.

Systematic review of the costeffectiveness of LVADs for people

with ESHF
Nineteen studies assessed the costs and costeffectiveness of LVADS for people with ESHF, with
the majority being simple costing studies and very
few studies of the cost-effectiveness of LVADs. A
number of the costing studies had serious
methodological flaws. Even those judged of
higher quality had caveats limiting applicability
and generalisability to a UK population.
Significant limitations were the limited sample size
and the lack of comparators against which to
judge the significance of the reported costs. There
was only one UK-based costutility analysis, which
was populated with costs based on treatment
protocols, data from individual NHS Trust finance
departments and utilities derived from a US base
study. The UK study reported cost per qualityadjusted life-year (QALY) values at the boundary
of acceptability given recent decision-making.
Based on total treatment costs of both LVAD BTT
support and heart transplantation, the discounted
cost per QALY was approximately 39,790 (range
28,51074,000). Threshold analysis found that an
LVAD device and procedure cost of 19,300 would
equate to a cost per QALY of 20,000 or less.

Economic evaluation to assess

the cost-effectiveness of LVADs for
people with ESHF within the UK
The economic evaluation has shown that neither
LVAD indication considered, that is, BTT and
LTCS, is a cost-effective use. For the HeartMate
LVAD used as a BTT the cost per QALY was
65,242. Stochastic simulation calculated the 95%
confidence interval at 34,194 to 364,564. Only
when the survival gain falls significantly does the
cost-effectiveness rise to such upper bounds. A
cost-effectiveness acceptability curve showed the
likelihood of acceptability at current costeffectiveness thresholds. The BTT indication
approaches cost-effectiveness only when the oneoff costs associated with an LVAD fall considerably.
At a combined LVAD device and operation cost of
50,000 (compared with 87,877 in our model),
the cost per QALY fell to approximately 40,000.
Unfortunately, even assuming this eventuality, the
BTT indication use parallels an ever-decreasing
supply of donor hearts capping the ability of this
innovative technology to yield widespread benefit.
In the less restrictive indication, LTCS, where
LVADs are not just given to patients awaiting
transplantation, the analysis has shown that LTCS
is not cost-effective. The baseline cost per QALY
of the first-generation HeartMate LVAD was
170,616. One- and multi-way sensitivity analysis

Health Technology Assessment 2005; Vol. 9: No. 45 (Executive summary)

had limited effect on the cost per QALY. A

hypothetical scenario based on the cost of a
second-generation MicroMed DeBakey device
illustrated that a 60% improvement in survival
over first-generation devices was necessary before
the incremental cost-effectiveness approached
40,000 per QALY. Although the analyses
recognise the benefits in terms of survival and
quality of life, these are outweighed by associated
increases in cost. Uncertainties remain,
particularly with the lack of trial data on LTCS,
research on second-generation devices and
ongoing costs of medical management. The use of
expert-based utilities in the LTCS data is also
innovative but the sensitivity testing has shown this
not to be an influential factor on cost-effectiveness
at the margin.

Discussion and conclusions

Implications for practice
Although the systematic review of clinical
effectiveness showed that LVADs are clinically
effective as a BTT for people with ESHF, the
economic evaluation indicated that they are not
cost-effective. With the limited and declining
availability of donor hearts for transplantation, it
appears that the future of the technology is in its
use as an LTCS. At present the evidence of clinical
and cost-effectiveness of LVADs as an LTCS is less
certain, particularly for the second-generation
devices, and further study is needed. The limited
research available showed some clinical benefit for
patients receiving LVADs as an LTCS, but the
economic evaluation suggested that they were not
a cost-effective option. Limited numbers of
patients with ESHF receive an LVAD within
England and Wales and uncertainty remains about
the potential need and demand that may exist. As
a consequence, it is likely that there will be limited
availability of clinical teams who can undertake
these procedures and manage the patients
subsequently and there would need to be a rapid
increase in the training of staff and a step change

in the development of the necessary infrastructure.

To provide the service to meet the needs of
a conservative estimate of 3000 patients would
result in a discounted cost to the NHS annually of
321 million. With less conservative estimates
putting the potential need at between 7000 and
34,000 patients, the actual cost may be far higher.

Recommendations for future research

Although LVADs appear to be effective in
improving the survival of patients with ESHF,
whether as a BTT, BTR or LTCS, the
methodological quality and strength of the
evidence are poor. Further research is needed to
examine the clinical effectiveness of LVADs for
people with ESHF, assessing patient survival,
functional ability, quality of life and adverse
events. Although difficult to undertake with such
fast-changing technologies, such evaluations
should be RCTs and look at the head-to-head
comparisons of different devices or usual medical
care. Importantly, these studies should encompass
the breadth of patient groups that may benefit
from these devices. Evaluations of the clinical
effectiveness of LVADs should include economic
evaluations. It has become evident from this study
that data for undertaking such studies are very
limited. Data on quality of life, utilities, resources
and costs are not readily available. Also, there is
limited research on the epidemiology of ESHF
and, as a consequence, it is difficult to establish
the possible need and demand for the service. A
systematic review of the epidemiology of ESHF
should be undertaken to assess its potential
impact.

Publication
Clegg AJ, Scott DA, Loveman E, Colquitt J,
Hutchinson J, Royle P, et al. The clinical and
cost-effectiveness of left ventricular assist devices
for end-stage heart failure: a systematic review
and economic evaluation. Health Technol Assess
2005;9(45).

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